IN-DEPTH: REPRODUCTIVE ENDOCRINOLOGY


feedback effects of altrenogest. Often, when dis- continuing altrenogest treatment, veterinarians will gradually lower, over a week or so, the daily altreno- gest dose administered before its complete cessation. The theory behind this “weaning” practice is that it will allow time for the gravid mare’s endogenous endocrine systems to gradually adapt to altrenogest withdrawal. Endotoxin experiments provided good evidence


for the practical use of altrenogest supplementation during early pregnancy, before formation of endo- metrial cups, in the mare.15 Endotoxin stimulates endogenous prostaglandin release, thus causing lu- teolysis, with resulting pregnancy loss. Mares be- tween 21 to 35 days of pregnancy were administered systemic endotoxin. All seven mares that were con- comitantly administered 44 mg of altrenogest orally once daily until day 70 maintained their pregnan- cies. In mares that were administered altrenogest only to day 40 of gestation, six of seven mares had fetal death within 4 days of altrenogest cessation. Thus, altrenogest administered at the time of insult could maintain early pregnancy despite a toxic in- sult and subsequent luteolysis. In addition, the al- trenogest treatment needed to be maintained until the feto-placental unit was producing adequate pro- gestogen for subsequent pregnancy maintenance. The 44 mg of altrenogest per mare used in this study corresponds to a dose of approximately 0.088 mg/kg, which is commonly called a “double dose.”15 By com- parison, the standard dose of altrenogesta labeled for suppressing estrus is 0.044 mg/kg (“single dose”) orally every 24 hours.16 These same researchers also addressed whether flunixin meglumine could prevent luteolysis and maintain pregnancy in mares that were adminis- tered endotoxin.17 Flunixin meglumine, a non-ste- roidal anti-inflammatory cyclo-oxygenase inhibitor, interferes with the production of prostaglandin. When flunixin meglumine was administered to mares between days 21 and 44 of gestation intra- venously 10 minutes before endotoxin adminis- tration, endogenous progesterone production was maintained and none of the seven mares lost their pregnancy. In those mares in which flunixin me- glumine was administered 1 hour after endotoxic insult, systemic progesterone fell to below 2 ng/mL for several days, and pregnancy was lost in one of three mares. When flunixin meglumine was ad- ministered 2 hours after endotoxic insult, proges- terone fell to below 0.5 ng/mL, and all three pregnancies were lost. Likewise, the 12 pregnant mares administered only endotoxin had very low progesterone concentrations, and all lost their preg- nancies. Thus, flunixin meglumine was most use- ful when administered before endotoxin was given, but it was also of benefit in maintaining pregnancy in two of three mares when administered within 1 hour of the insult.17 Other work supports the administration of pro- gesterone or altrenogest to maintain pregnancy


in the face of prostaglandin-induced abortion. In one study, six mares between 82 and 102 days of gestation were administered 250 g of clopros- tenol (q 24 h, IM) to induce abortion.18 Systemic prostaglandin concentrations rose, whereas proges- terone concentrations fell, and fetuses were expelled spontaneously by the third day of cloprostenol ad- ministration.18 Subsequently, the ability of pro- gesterone or altrenogest19 and flunixin meglumine20 administration to inhibit abortion induced by clopro- stenol administration was examined. Mares were either administered progesterone 300 mg (q 24 h, IM) or 44 mg altrenogest (q 24 h, PO; “double dose”) beginning either 18 or 12 hours, respectively, after the first cloprostenol injection. The progesterone regimen was used in eight mares between 98 to 153 days of gestation, and, of these mares, only three aborted. When altrenogest was used in similar fashion in mares between 93 to 115 days of gesta- tion, none of the mares aborted.19 In contrast, when 500 mg flunixin (q 8 h, IV) was administered beginning 15 minutes before the first daily clo- prostenol injection, all mares aborted.20 Thus, pro- gesterone or altrenogest supplementation19 but not flunixin administration20 blocked cloprostenol- induced abortion at these gestational ages. Taken together, these studies support the concept that progestin supplementation can maintain equine pregnancy when the mares were submitted to pros- taglandin F2insults.15,19 If there is fetal demise after formation of the en- dometrial cups, the mare will normally have a phase of pseudopregnancy.1 Even without a live preg- nancy, the endometrial cups will not regress until approximately days 120 to 150 after ovulation. The cups continue to secrete eCG, subsequently causing the ovarian luteal structures to secrete pro- gesterone, which inhibits resumption of cyclicity. Loss of pregnancy during the endometrial cup phase will generally prevent the mare from becoming preg- nant again during that season. Therefore, in cases in which a pregnancy must be terminated early (ie, presence of twins), it is important to perform elective abortion before endometrial cup formation, which is approximately 35 days of gestation but subject to individual mare variation. Before eCG production, a single dose of prostaglandin adminis- tered to the pregnant mare will result in luteolysis and pregnancy termination. Return to estrus and ovulation are normal after this procedure when performed before the eCG phase. After eCG pro- duction is present, and hence after the formation of supplementary corpora lutea, multiple doses of pros- taglandin are necessary to terminate pregnancy. Although some mares may return to estrus when fetal demise (termination or spontaneous) occurs during the eCG phase, others will not. The eCG production that continues after the fetal loss affects ovarian function, in which case follicles develop but then may luteinize, without ovulating properly.1


AAEP PROCEEDINGS  Vol. 59  2013 353


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